**17. CREST trial**

years of follow-up was higher with stenting than with endarterectomy (11 1% vs. 6 2%, hazard ratio [HR] 1 97, 95% CI 1 06–3 67; p=0 03). The HR for periprocedural disabling stroke or death and non-procedural fatal or disabling ipsilateral stroke was 2 00 (0 75–5 33; p=0 17). A hazard function analysis showed the 4-year differences in the cumulative probabilities of outcomes between stenting and endarterectomy were largely accounted for by the higher periprocedural (within 30 days of the procedure) risk of stenting compared with endarterectomy. After the periprocedural period, the risk of ipsilateral stroke was low and similar in both treatment groups. For any stroke or periprocedural death, the HR was 1 77 (1 03–3 02; p=0 04). For any stroke or death, the HR was 1 39 (0 96–2 00; p=0 08). The results of this study suggest that carotid stenting is as effective as carotid endarterectomy for middle-term prevention of ipsilateral stroke, but the safety of carotid stenting needs to be improved before it can be used as an alternative to carotid endarterectomy in patients with symptomatic carotid stenosis.[22] In the same study, the rate of carotid restenosis of ≥50% or occlusion was significantly higher after CAS (12.5%) than after CEA (5.0%; time ratio, 0.16; 95% CI, 0.03–0.76; *P*=0.02). The rates of severe restenosis of ≥70% or occlusion were low and did not differ significantly between the 2 groups (3-year rates are 3.3% in the CAS group and 2.8% in the CEA group). Age at baseline was the only vascular risk factor significantly associated with carotid restenosis. Our study

could not detect any effect of carotid restenosis on ipsilateral stroke.[23]

RR 2.04, 1.48–2.82, interaction p = 0.0053).[25]

114 Carotid Artery Disease - From Bench to Bedside and Beyond

stroke recurrence.[25]

**16. ICSS study**

It was notable that the risk of ipsilateral stroke or death increased significantly with age in the CAS group (p=0 001) but not in the CEA group (p=0 534). Classification and regression tree analysis showed that the age that gave the greatest separation between high-risk and low-risk populations who had CAS was 68 years: the rate of primary outcome events was 2 7% (8/293) in patients who were 68 years old or younger and 10 8% (34/314) in older patients.[24]

In the first 120 days after randomization (ITT analysis), the primary outcome event occurred in 153/1725 patients in the CAS group (8.9%) compared with 99/1708 patients in the CEA group (5.8%, risk ratio [RR] 1.53, 95% confidence interval [CI] 1.20–1.95, p = 0.0006; absolute risk difference 3.2, 95% CI 1.4–4.9). Age was the only subgroup variable which significantly modified the treatment effect: in patients <70 years old (the median age), the 120-day stroke or death risk was 5.8% in CAS and 5.7% in CEA (RR 1.00, 0.68–1.47); in patients 70 years or older, there was an estimated two-fold increase in risk with CAS over CEA (12.0% vs. 5.9%,

Endarterectomy was safer in the short-term than stenting, because of an increased risk of stroke associated with stenting in patients over the age of 70 years. Stenting should be avoided in older patients, but may be as safe as endarterectomy in younger patients. Determination of the efficacy and ultimate balance between the two procedures requires further data on long-term

The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs. 44 events; HR 1.69, 1.16-2.45, The CREST (Carotid Revascularization Endarterectomy vs. Stent Trial) was a multicenter trial supported by the National institute of health. The study includes symptomatic (>50% stenosis) and asymptomatic (>70% stenosis) patients. The CREST was probably the largest study on carotid revascularization and had the best design. Centers were required to have a team consisting of a neurologist, an interventionist, a surgeon, and a research coordinator. Patients could not be randomly assigned to a treatment group until the operators performing carotid artery stenting and carotid endarterectomy had been certified. Certification was achieved by 477 surgeons, whose clinical results were audited by means of a validated selection process documenting that they performed more than 12 procedures per year and that the rates of complications and death were less than 3% among asymptomatic patients and less than 5% among symptomatic patients. The 224 interventionists were certified after satisfactory evaluation of their endovascular experience, carotid-stenting results, participation in handson training, and participation in a lead-in phase of training.[28]

There was no differential treatment effect with regard to the primary end point according to symptomatic status (P = 0.84) or sex (P = 0.34). The 4-year rate of stroke or death was 6.4% with stenting and 4.7% with endarterectomy (hazard ratio, 1.50; P = 0.03); the rates among symp‐ tomatic patients were 8.0% and 6.4% (hazard ratio, 1.37; P = 0.14), and the rates among asymptomatic patients were 4.5% and 2.7% (hazard ratio, 1.86; P = 0.07), respectively. Peri‐ procedural rates of individual components of the end points differed between the stenting group and the endarterectomy group: for death (0.7% vs. 0.3%, P = 0.18), for stroke (4.1% vs. 2.3%, P = 0.01), and for myocardial infarction (1.1% vs. 2.3%, P = 0.03). After this period, the incidences of ipsilateral stroke with stenting and with endarterectomy were similarly low (2.0% and 2.4%, respectively; P = 0.85).[28]

radiation. The only analyzed variables that were significantly associated with an increased risk of restenosis were previous CEA (OR 4.28, P = 0.008) or XRT (OR 11.3, P <or=<or= 0.0001).[33] In another study, among 215 CAS procedures that had clinical and serial carotid duplex ultrasound investigations, restenosis was detected in 6.1% of patients. Contralateral carotid occlusion (OR 10.11, 95% CI 2.06-49.63, p = 0.004), carotid endarterectomy (CEA) restenosis (OR 8.87, 95% CI 1.68-46.84, p = 0.010) and postprocedural carotid duplex ultrasound with a PSV >/=120 cm/s (OR 6.33, 95% CI 1.27-31.44, p = 0.024) were independent predictors of stent restenosis.[34] Most restenoses occur within 6 to 12 months after the intervention. Usually they are located either in the mid or at the distal end of the stent. Restenoses are often overestimated by ultrasound compared to angiography. Most of restenoses can be treated by balloon angioplasty. Drug-eluting balloons can be a promising modality[35] and only rarely, stent

Update on Carotid Revascularization: Evidence from Large Clinical Trials

http://dx.doi.org/10.5772/57153

117

The incidence ranges from 1.2% to 23.9% depending on the operative technique. The highest rates of restenosis, 21.4%, after CEA came with direct suture and the lowest rate 3.9% were after patch angioplasty only Long-term risk of recurrence is about 1% per year. The risk is highest in the first few years after CEA and is very low later.[37]. Most of restenoses are

The type of operative technique for reoperations depends on the cause of the recurrent disease. Myointimal hyperplasia has a smooth luminal surface and appears to be associated with a low potential for embolization therefore simple patching may be all that is necessary. By contrast, the soft nature of the plaque in recurrent atherosclerosis, which appears later, has a greater potential for embolization therefore repeat CEA with carotid patch angioplasty is preferable. AbuRahma et al showed the 30-day perioperative stroke and transient ischemic attack rates for reoperation and primary CEA were 4.8% versus 0.8% (P=0.015) and 4% versus 1.1%, respectively. There was an increase in the number of transient cranial nerve injuries in the

reoperation group compared with the primary CEA group (15.3% versus 4.9%).[39]

**18.3. Carotid stenosis in patients requiring bypass cardiac surgery**

of stroke after CABG ranges from 0.7-5.2%[42]

CAS for restenosis after CEA has a complication rate lower than primary CAS. The time interval between CEA and CAS did not influence micro embolic load.[40] Statistical analysis demonstrated that post-CEA restenosis was the most important predictive factor for the development of in-stent restenosis after CAS. This review of our 10-year experience confirms that patients who develop restenosis after CEA are also prone to developing in-stent restenosis

Patients who have concomitant severe carotid and coronary artery disease pose a serious dilemma. Stroke remains a major non-cardiac complication after CABG and myocardial infarction is the major non-neurological cause of early and late morbidity after CEA. The risk

removal and eversion endarterectomy will be required.[36]

asymptomatic and only 1.2-3.6% require re-intervention.[38]

**18.2. Restenosis after carotid endarterectomy**

after CAS.[41]

The results of the CREST were "satisfying" for both surgeons and interventionists. Surgeons were glad to prove that CEA resulted in lower stroke rates in the short term and the long term. Interventionists were reassured that the primary end-point was similar in the two methods.

Restenosis and occlusion were infrequent and rates were similar up to 2 years after carotid endarterectomy and carotid artery stenting. Subsets of patients could benefit from early and frequent monitoring after revascularization.[29]

CAS was associated with better health-related quality of life HRQOL during the early recovery period as compared with CEA-particularly with regard to physical limitations and pain-but these differences diminish over time and are not evident after 1 year. Although CAS and CEA are associated with similar overall quality of life at 1 year, event-specific analyses confirm that stroke has a greater and more sustained impact on HRQOL than MI.[30]

The MI rates were slightly lower after CAS (1.3% vs. 2.6%; P =.24). In performing CAS, vascular surgeons had outcomes for the periprocedural primary end point comparable to the outcomes of all interventionists (HR, 0.99; 95% CI, 0.50-2.00) after adjusting for age, sex, and symptomatic status. Vascular surgeons also had similar results after CEA for the periprocedural primary end point compared with other surgeons (HR, 0.73; 95% CI, 0.42-1.27).[31]
